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Scandinavian Journal of Pain Jan 2023Peripheral neuropathies that occur secondary to nerve injuries may be painful or painless, and including a low-grade inflammation and pro-inflammatory cytokines...
OBJECTIVES
Peripheral neuropathies that occur secondary to nerve injuries may be painful or painless, and including a low-grade inflammation and pro-inflammatory cytokines associated with both regeneration and damage of peripheral nerve cells and fibers. Currently, there are no validated methods that can distinguished between neuropathic pain and painless neuropathy. The aim of this study was to search for proinflammatory and anti-inflammatory proteins associated with pain and experimental pain sensitivity in subjects with surgeon-verified nerve injuries in the upper extremities.
METHODS
One hundred and thirty-one subjects [69 with neuropathic pain, NP; 62 with painless neuropathy, nP] underwent a conditioned pain modulation (CPM) test that included a cold pressor task (CPT) conducted with the non-injured hand submerged in cold water (4 °C) until pain was intolerable. CPM was assessed by pain ratings to pressure stimuli before and after applying the CPT. Efficient CPM effect was defined as the ability of the individual's CS to inhibit at least 29% of pain (eCPM). The subjects were assigned to one of two subgroups: pain sensitive (PS) and pain tolerant (PT) after the time they could tolerate their hand in cold water (PS<40 s and PT=60 s) . Plasma samples were analyzed for 92 proteins incorporated in the inflammation panel using multiplex Protein Extension Array Technology (PEA). Differentially expressed proteins were investigated using both univariate and multivariate analysis (principal component analysis-PCA and orthogonal partial least-squares discriminant analysis-OPLS-DA).
RESULTS
Significant differences in all protein levels were found between PS and PT subgroups (CV-ANOVA p<0.001), but not between NP and nP groups (p=0.09) or between inefficient CPM (iCPM) and eCPM (p=0.53) subgroups. Several top proteins associated with NP could be detected using multivariate regression analysis such as stromelysin 2 (MMPs), interleukin-2 receptor subunit beta (IL2RB), chemokine (C-X-C motif) ligand 3 (CXCL3), fibroblast growth factor 5 (FGF5), chemokine (C-C motif) ligand 28 (CCL28), CCL25, CCL11, hepatocyte growth factor (HGF), interleukin 4 (IL4), IL13. After adjusting for multiple testing, none of these proteins correlated significantly with pain. Higher levels of CCL20 (p=0.049) and CUB domain-containing protein (CDCP-1; p=0.047) were found to correlate significantly with cold pain sensitivity. CDCP-1 was highly associated with both PS and iCPM (p=0.042).
CONCLUSIONS
No significant alterations in systemic proteins were found comparing subjects with neuropathic pain and painless neuropathy. An expression of predominant proinflammatory proteins was associated with experimental cold pain sensitivity in both subjects with pain and painless neuropathy. One these proteins, CDC-1 acted as "molecular fingerprint" overlapping both CPM and CPT. This observation might have implications for the study of pain in general and should be addressed in more detail in future experiments.
Topics: Humans; Ligands; Pain Measurement; Pain Threshold; Neuralgia; Inflammation
PubMed: 35531763
DOI: 10.1515/sjpain-2021-0195 -
Fertility and Sterility Nov 2018To investigate alterations in tactile, pain thresholds and pain tolerance thresholds in patients with endometriosis using a multimodality approach.
OBJECTIVE
To investigate alterations in tactile, pain thresholds and pain tolerance thresholds in patients with endometriosis using a multimodality approach.
DESIGN
Cross-sectional study.
SETTING
Multidisciplinary referral center.
PATIENT(S)
Women with proven endometriosis (N = 35) and healthy controls (N = 38).
INTERVENTION(S)
Pain processing was tested using quantitative sensory testing (QST) to investigate sensation, pain, and pain tolerance thresholds for thermal, electrical, and pressure stimuli.
MAIN OUTCOME MEASURE(S)
Differences in QST measures in patients with endometriosis and in healthy controls on the endometriosis site and control sites, and the association between QST outcomes and patient characteristics.
RESULT(S)
We observed a significantly decreased pain tolerance in patients with endometriosis, independent of clinical pain intensity or revised American Society for Reproductive Medicine stage, compared with healthy controls.
CONCLUSION(S)
Increasing knowledge concerning mechanisms underlying the pain of women with endometriosis creates opportunities to develop new treatment options. More attention should be paid not only to treat endometriosis in a surgical or pharmacologic way, but also to desensitize by pain education or cognitive therapy.
Topics: Adolescent; Adult; Cross-Sectional Studies; Endometriosis; Female; Humans; Middle Aged; Pain; Pain Measurement; Pain Threshold; Young Adult
PubMed: 30396556
DOI: 10.1016/j.fertnstert.2018.06.040 -
Pain Research & Management 2023Pain sensitivity decreases following isometric exercise. It is not clear whether this exercise-induced hypoalgesia (EIH) occurs to the same extent in men and women. It...
OBJECTIVE
Pain sensitivity decreases following isometric exercise. It is not clear whether this exercise-induced hypoalgesia (EIH) occurs to the same extent in men and women. It is also unclear if the effect is systemic or local to the exercised musculature. The aim of our study was to investigate whether fatiguing isometric exercise of the spinal and hip extensors would result in increased pressure pain threshold (PPT) at sites local to and remote from the exercised muscles in healthy men and women and whether there is a relationship between central sensitization, psychosocial factors, and PPT.
SUBJECTS
35 healthy adults (age 27.1 ± 4.5 years, 22 women).
METHODS
This was a within-subjects cohort study. Participants completed questionnaires quantifying central sensitization, pain catastrophizing, sleepiness/insomnia, anxiety, and depression. PPT was assessed at the lumbar and thoracic paraspinals, hamstrings, gastrocnemius, wrist, and third digit before and immediately after participants performed the Biering-Sorensen test to failure.
RESULTS
PPT increased postexercise in the thoracic paraspinals, hamstrings, and gastrocnemius in men and women and in the lumbar paraspinals in men only but did not change at the wrist and digit sites. A lower average PPT at baseline was associated with a higher central sensitization scores. A greater increase in average PPT postfatigue was significantly associated with higher average PPT at baseline.
CONCLUSIONS
Exercise-induced hypoalgesia occurs at sites overlying the muscles involved in fatiguing exercise, but not at remote sites, and is more evident in males than females. The magnitude of EIH depends upon baseline PPT. Even in healthy individuals, greater central sensitization is associated with lower baseline PPT.
Topics: Male; Adult; Humans; Female; Young Adult; Pain Threshold; Muscle Fatigue; Cohort Studies; Pain Measurement; Isometric Contraction; Pain; Hypesthesia
PubMed: 36741677
DOI: 10.1155/2023/7336477 -
Chiropractic & Manual Therapies Oct 2020Assessing the responses of body tissue subjected to mechanical load is a fundamental component of the clinical examination, psychophysical assessments and bioengineering... (Review)
Review
Assessing the responses of body tissue subjected to mechanical load is a fundamental component of the clinical examination, psychophysical assessments and bioengineering research. The forces applied during such assessments are usually generated manually, via the hands of the tester, and aimed at discreet tissue sites. It is therefore desirable to objectively quantify and optimise the control of manually applied force. However, current laboratory-grade manual devices and commercial software packages, in particular pressure algometer systems, are generally inflexible and expensive. This paper introduces and discusses several principles that should be implemented as design goals within a flexible, generic software application, given currently available force measurement hardware. We also discuss pitfalls that clinicians and researchers might face when using current pressure algometer systems and provide examples of these. Finally, we present our implementation of a pressure algometer system that achieves these goals in an efficient and affordable way for researchers and clinicians. As part of this effort, we will be sharing our configurable software application via a software repository.
Topics: Animals; Humans; Pain Measurement; Pain Threshold; Physical Examination; Pressure; Software
PubMed: 33012288
DOI: 10.1186/s12998-020-00340-7 -
The Clinical Journal of Pain Jul 2022The aim of this study was to investigate if somatosensory profiles can differentiate pain and psychophysiological symptoms among young adults with irritable bowel... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The aim of this study was to investigate if somatosensory profiles can differentiate pain and psychophysiological symptoms among young adults with irritable bowel syndrome (IBS).
METHODS
We performed a cluster analysis of data collected from a randomized clinical trial of 80 IBS patients and 21 age-matched healthy controls (HCs) to stratify pain and symptoms among young adults with IBS by their peripheral sensory profiles. Data of quantitative sensory testing and IBS-related pain and symptoms were collected at baseline and 6-week and 12-week follow-ups.
RESULTS
Using the K-means method, IBS patients were classified into 2 clusters, the "IBS normal threshold" (IBS-NT) and the "IBS increased threshold" (IBS-IT). The IBS-NT cluster had a similar pain threshold as the HCs, and the IBS-IT cluster had an increased threshold of somatic pain perception (lower cold pain threshold, higher heat pain threshold, and higher pressure pain threshold, all P<0.001) than HCs. Compared with the IBS-NT cluster, the IBS-IT cluster reported higher levels of IBS-related pain intensity, anxiety, fatigue, and sleep disturbance over the 3 visits (all P<0.05).
DISCUSSION
Young adults with IBS fell into 2 clusters, one with a similar sensory threshold as the HCs and another with an increased pain threshold, who reported higher pain intensity and more severe symptoms. Somatic sensory profiles should be integrated into further personalized self-management intervention among patients with IBS.
Topics: Cluster Analysis; Humans; Irritable Bowel Syndrome; Nociceptive Pain; Pain Measurement; Pain Threshold; Young Adult
PubMed: 35686579
DOI: 10.1097/AJP.0000000000001046 -
Pain Medicine (Malden, Mass.) Jan 2018The purpose of this study was to examine the interaction between the endogenous opioid and endocannabinoid (eCB) systems in a pain modulatory process known as... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The purpose of this study was to examine the interaction between the endogenous opioid and endocannabinoid (eCB) systems in a pain modulatory process known as exercise-induced hypoalgesia (EIH).
DESIGN
Randomized controlled trial.
SETTING
Clinical research unit in a hospital.
SUBJECTS
Fifty-eight healthy men and women (mean age = 21 ± 3 years) participated in this study.
METHODS
Participants were administered (randomized, double-blind, counterbalanced procedure) an opioid antagonist (i.e., naltrexone) and a placebo prior to performing pain testing and isometric exercise.
RESULTS
Results indicated that 2-arachidonoylglycerol (2-AG) and 2-oleoylglycerol (2-OG) increased significantly (P < 0.05) following exercise in both placebo and naltrexone conditions. In comparison, N-arachidonylethanolamine (AEA) and oleoylethanolamine (OEA) increased significantly (P < 0.05) following exercise in the placebo condition but not the naltrexone condition. There were no significant (P > 0.05) differences in palmitolethanolamine (PEA) between the placebo and naltrexone conditions.
CONCLUSIONS
As reductions in pain (i.e., EIH) were observed following both conditions, these results suggest that the opioid system may not be the primary system involved in exercise-induced hypoalgesia and that 2-AG and 2-OG could contribute to nonopioid exercise-induced hypoalgesia. Moreover, as exercise-induced increases in AEA and OEA were blocked by naltrexone pretreatment, this suggests that the opioid system may be involved in the increase of AEA and OEA following exercise.
Topics: Double-Blind Method; Endocannabinoids; Exercise; Female; Humans; Male; Naltrexone; Narcotic Antagonists; Pain Perception; Pain Threshold; Young Adult
PubMed: 28387833
DOI: 10.1093/pm/pnx058 -
The Journal of Pain Jan 2023Painful HIV-associated neuropathy (HIV-SN) is a prevalent co-morbidity of HIV infection. Sensory phenotyping, using quantitative sensory testing (QST) could allow for... (Observational Study)
Observational Study
Painful HIV-associated neuropathy (HIV-SN) is a prevalent co-morbidity of HIV infection. Sensory phenotyping, using quantitative sensory testing (QST) could allow for improved stratification to guide personalized treatment. However, previous methods of QST interpretation have demonstrated limited association with self-reported pain measures. This study sought to identify differences in self-reported pain measures between composite QST-derived sensory phenotypes, and to examine any differences in participants reporting multi-site, multi-etiology chronic pain. In this cross-sectional observational study of participants with HIV (n = 133), individuals were allocated to neuropathy and neuropathic pain groups through clinical assessment and nerve conduction testing. They completed symptom-based questionnaires and underwent standardized QST. Participants were assigned, by pre-determined algorithm, to a QST-derived sensory phenotype. Symptoms were compared between sensory phenotypes. Symptom characteristics and Neuropathic Pain Symptom Inventory scores differed between QST-derived sensory phenotypes: 'sensory loss' was associated with more paroxysmal and paraesthetic symptoms compared to 'thermal hyperalgesia' and 'healthy' phenotypes (P = .023-0.001). Those with painful HIV-SN and additional chronic pain diagnoses were more frequently allocated to the 'mechanical hyperalgesia' phenotype compared to those with painful HIV-SN alone (P = .006). This study describes heterogeneous sensory phenotypes in people living with HIV. Differences in self-reported pain outcomes between sensory phenotypes has the potential to guide future stratified trials and eventually more targeted therapy. PERSPECTIVE: This article presents quantitative sensory testing derived phenotypes, thought to reflect differing pathophysiological pain mechanisms and relates them to self-reported pain measures in people with HIV infection. This could help clinicians stratify patients to individualize analgesic interventions more effectively.
Topics: Humans; Hyperalgesia; Self Report; HIV Infections; Pain Measurement; Chronic Pain; Cross-Sectional Studies; Neuralgia; Phenotype; Pain Threshold
PubMed: 36116766
DOI: 10.1016/j.jpain.2022.09.005 -
Scandinavian Journal of Pain Jul 2021The expression of pain in males and females involves complex socio-psychological mechanisms. Males may report lower pain to a female experimenter to appear strong,...
OBJECTIVES
The expression of pain in males and females involves complex socio-psychological mechanisms. Males may report lower pain to a female experimenter to appear strong, whereas females may report higher pain to a male experimenter to appear weak and to seek protection. However, evidence to support these stereotypes is inconclusive. Individuals who catastrophise about pain rate higher pain than those who do not. How pain catastrophising interacts with the effect of the experimenter's sex on pain reports is yet to be explored. Thus, the aim of this study was to determine whether pain catastrophising moderated the effect of the experimenter's sex on pain reports in healthy males and females.
METHODS
Participants (n=60, 30 males) were assigned to one of four experimental conditions: males tested by male experimenters, males tested by female experimenters, females tested by male experimenters, and females tested by female experimenters. Participants completed the Pain Catastrophising Scale, and then sensitivity to heat and to blunt (pressure-pain threshold) and sharp stimuli was assessed on both forearms, and to high frequency electrical stimulation (HFS) administered to one forearm.
RESULTS
Females reported lower pressure-pain thresholds than males irrespective of the experimenters' sex. Females reported lower sharpness ratings to male than female experimenters only when the test stimuli were moderately or intensely sharp. Higher pain catastrophising scores were associated with higher sharpness ratings in females but not males. Additionally, higher pain catastrophising scores were associated with greater temporal summation of pain to HFS, and with lower pressure-pain thresholds in females who were tested by male experimenters.
CONCLUSIONS
These findings indicate that the experimenters' sex and the participant's pain catastrophising score influence pain reports, particularly in females. Awareness of these psychosocial factors is important in order to interpret pain responses in a meaningful way, especially when females are tested by male experimenters. A greater awareness of sex/gender role biases and their potential interaction with pain catastrophising may help researchers and clinicians to interpret pain reports in meaningful ways. In turn, this may help to improve delivery of treatments for patients with chronic pain.
Topics: Chronic Pain; Female; Forearm; Humans; Male; Pain Measurement; Pain Threshold
PubMed: 33565286
DOI: 10.1515/sjpain-2020-0157 -
PloS One 2021To determine the absolute and relative intra-rater within-session test-retest reliability of pressure pain threshold (PPT) and mechanical temporal summation of pain...
OBJECTIVE
To determine the absolute and relative intra-rater within-session test-retest reliability of pressure pain threshold (PPT) and mechanical temporal summation of pain (TSP) at the low back and the forearm in healthy participants and to test the influence of the number and sequence of measurements on reliability metrics.
METHODS
In 24 participants, three PPT and TSP measures were assessed at four sites (2 at the low back, 2 at the forearm) in two blocks of measurements separated by 20 minutes. The standard error of measurement, the minimal detectable change (MDC) and the intraclass correlation coefficient (ICC) were investigated for five different sequences of measurements (e.g. measurement 1, 1-2, 1-2-3).
RESULTS
The MDC for the group (MDCgr) for PPT ranged from 28.71 to 50.56 kPa across the sites tested, whereas MDCgr for TSP varied from 0.33 to 0.57 out of 10 (numeric scale). Almost all ICC showed an excellent relative reliability (between 0.80 and 0.97), except when only the first measurement was considered (moderate). Although minimal differences in absolute PPT reliability were present between the different sequences, in general, using only the first measurement increase measurement error. Three TSP measures reduced the measurement error.
DISCUSSION
We established that two measurements of PPT and three of TSP reduced the measurement error and demonstrated an excellent relative reliability. Our results could be used in future pain research to confirm the presence of true hypo/hyperalgesia for paradigms such as conditioned pain modulation or exercise-induced hypoalgesia, indicated by a change exceeding the measurement variability.
Topics: Adult; Back; Female; Forearm; Healthy Volunteers; Humans; Male; Pain; Pain Measurement; Pain Threshold; Pressure; Young Adult
PubMed: 33434233
DOI: 10.1371/journal.pone.0245278 -
Neuroscience Bulletin Apr 2018Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a...
Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a high-fat diet, we found that: (1) the acute thermal pain sensory threshold did not change in obese mice; (2) the model obese mice had fewer nociceptive responses in formalin-induced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation; (3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice, indicating the dysmodulation of topical leptin-leptin receptor signaling in these mice; and (4) leptin-leptin receptor signaling-deficient mice (ob/ob and db/db) or leptin-leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wild-type mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin-leptin receptor pathway could be a peripheral target against acute inflammatory pain.
Topics: Animals; Diet, High-Fat; Inflammation; Leptin; Male; Mice; Mice, Inbred C57BL; Nociception; Nociceptive Pain; Obesity; Pain Measurement; Pain Threshold; Receptors, Leptin; Signal Transduction
PubMed: 29204732
DOI: 10.1007/s12264-017-0194-2